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Hiroshi Nakamura
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P2.09 - Pathology (Not CME Accredited Session) (ID 958)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.09-25 - Abundant Tumor Promoting Stromal Cells in Lung Adenocarcinoma with Hypoxic Regions (ID 12409)
16:45 - 18:00 | Presenting Author(s): Hiroshi Nakamura
- Abstract
Background
Carbonic anhydrase IX (CAIX) is a marker of hypoxia and its expression by cancer associated fibroblasts (CAFs) was reportedly associated with the poor prognosis of lung adenocarcinoma. This study aimed to characterize the hypoxic microenvironment containing CAIX (+) CAFs.
a9ded1e5ce5d75814730bb4caaf49419 Method
First, we evaluated the clinicopathological significance of CAIX expression by CAFs in 3 cm and above lung adenocarcinoma (n = 188). We then compared the expressions of E-cadherin, ezrin, ALDH1, CD44, EGFR, HSF-1, Glut-1, and PD-L1 in cancer cells, as well as those of CD204 and podoplanin in stromal cells between CAIX (+) CAFs and CAIX (−) CAFs cases (n = 25, each).
4c3880bb027f159e801041b1021e88e8 Result
In total, 48 patients had CAIX (+) CAFs (26%). Multivariate analysis revealed that CAIX expression by CAFs could serve as an independent unfavorable prognostic factor for recurrence-free survival (p < 0.05). The staining score of hypoxia marker Glut-1 in cancer cells was significantly higher in cases with CAIX (+) CAFs than in those with CAIX (−) CAFs (median: 20 vs. 0, p < 0.01). In addition, the numbers of CD204 (+) tumor associated macrophages (TAMs) and podoplanin (+) CAFs were significantly higher in the CAIX (+) CAFs group than in the CAIX (−) CAFs group (TAMs: 31.5 vs. 17.0: p < 0.01, CAFs: 20 vs. 0: p < 0.05). The staining score of the other markers did not differ between the groups.
8eea62084ca7e541d918e823422bd82e Conclusion
Our results indicate that the presence of abundant tumor promoting stromal cells, CD204 (+) TAMs, and podoplanin (+) CAFs is characteristic of the tumor microenvironment containing CAIX (+) CAFs, which contributes to an increase in aggressive behavior in lung adenocarcinoma with hypoxic regions.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.09 - Pathology (Not CME Accredited Session) (ID 975)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.09-06 - The Link Between Tumor Promoting Fibrous Microenvironment and Immunosuppressive Microenvironment in Stage I Lung Adenocarcinoma (ID 14371)
12:00 - 13:30 | Author(s): Hiroshi Nakamura
- Abstract
Background
Podoplanin-positive cancer-associated fibroblasts (PDPN (+)CAFs) play an important role in cancer progression in non-small-cell lung cancer (NSCLC). The aim of this study is to clarify the correlation between fibrous microenvironment containing PDPN (+) CAFs and immune microenvironment.
a9ded1e5ce5d75814730bb4caaf49419 Method
174 cases with stage I primary lung adenocarcinoma were analyzed in this study. We evaluated PDPN (+) CAFs and immune-related cells; CD 204-positive tumor-associated macrophages (CD204 (+) TAMs); CD8-positive T cells; and FOXP3-positive T cells in cancer stroma by immunohistochemical staining method. By analyzing the gene expression profiles of lung adenocarcinoma (n=442), we compared the expression level of immune-regulatory cytokines between PDPN expression-high group and PDPN expression-low group.
4c3880bb027f159e801041b1021e88e8 Result
Presence of PDPN (+) CAFs was a risk factor for recurrence (P = 0.012). The number of CD204 (+) TAMs was significantly higher in PDPN (+) CAFs cases than in PDPN (+) CAFs cases (P < 0.001). Furthermore, CD8 (+)/FOXP3 (+) T cell ratio was significantly lower in PDPN (+) CAFs cases (P = 0.027). Within the same tumor, the number of CD 204 (+) TAMs was significantly higher in PDPN (+) CAFs area than in PDPN (-) CAFs area (P < 0.001). Moreover, CD8 (+)/FOXP3 (+) T cell ratio tend to be lower in PDPN (+) CAFs area than in PDPN (+) CAFs area (P = 0.062). Microarray analysis revealed PDPN expression-high group had significant higher levels of M-CSF; a cytokine inducing M2 macrophage polarization, and TGFβ1, IDO, VEGFA and galectin 1; immunosuppressive cytokines.
8eea62084ca7e541d918e823422bd82e Conclusion
The current results revealed that lung adenocarcinoma with PDPN (+) CAFs is typified by an immunosuppressive microenvironment, suggesting the close link between tumor promoting fibrous microenvironment and immune microenvironment.
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